A substantial number of untreated HIV-1 patients ultimately develop HIV-associated neurological diseases, including dementia (HAD). However, in sub-Saharan Africa, where the impact of the AIDS pandemic is most devastating, the total impact of HIV-associated neurological diseases is unknown. This represents a critical gap in scientific knowledge because almost two-thirds of the individuals living with HIV/AIDS reside in sub-Saharan Africa - a number of the countries in the region have infection rates to as high as 30 - 40% of their total population. Our long-term research goal is to understand the neuropathogenesis of HIV infection, the impacts of AIDS-associated neurological diseases and antiretroviral treatment on HAD in the African setting, and to design effective interventions to prevent or impede HAD development. However, the goal of this R21 planning grant application is to determine the impact and extent of HIV-associated neurological diseases in Zambia and to build the necessary in-country capacity for conducting HIV-1 neuropathogenesis research. The need for the proposed work is exacerbated by the fact that HIV-1 prevalence rate in Zambia is one of the highest in sub-Saharan Africa The proposed study represents a new direction for the participating investigators and leverages infrastructure established by the University of Nebraska-Lincoln, the University of Miami, the University of Zambia School of Medicine, and the University Teaching Hospital for research and training regarding HIV-1 and AIDS and their associated malignancies. The project goal will be achieved by completing three specific aims: 1) developing tools needed to evaluate the extent of HIV- associated neurological diseases in Zambia; 2) determining the prevalence and underlying pathology of HIV-associated dementia in subtype C infected individuals in Zambia; and 3) providing short-term training for Zambian neurologists, pathologists, and neurovirologists - both in-country and in the U.S. - to develop the tools and technology needed to address the first two proposed aims and to develop the neuroAIDS research infrastructure. The proposed work will lay the necessary foundation for a Zambian HIV-1 neuropathogenesis program by linking U.S. and Zambian partners, and by providing the necessary training and support to generate crucial preliminary data regarding the extent of HIV-associated neurological diseases in Zambia. The preliminary data collected as part of this effort will serve as the basis for a follow-up R01 application. [unreadable] [unreadable] [unreadable]